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Small molecules that enable cartilage rejuvenation

a small molecule and cartilage technology, applied in the direction of organic chemistry, organic active ingredients, drug compositions, etc., can solve the problems of limited cartilage regeneration in humans, osteoarthritis, and inability to regenerate cartilage, and achieve the effect of increasing the secretion of cartilaginous matrix in cartilag

Active Publication Date: 2021-07-27
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cartilage injury and minimal regeneration often lead to osteoarthritis, characterized by degradation of joints, including both articular cartilage and subchondral bone.
Although cartilage regeneration in humans is limited, recent clinical reports about cartilage healing in long term immobilized OA joints suggest that the regenerative potential of articular cartilage may be underestimated.
A variety of options exist for the treatment of cartilage lesions, most with limited results.
This technique, only performed for smaller lesions, results in the formation of fibrocartilage that has inferior mechanical properties as compared to hyaline cartilage.
Clear limitations exist for these procedures, including limited supply of donor cartilage, as well as significant donor site morbidity.
None of the current mesenchymal cell-based repair strategies including in vitro expanded adult mesenchymal stromal cells from bone marrow, adipose tissue, synovium or amniotic fluid have generated long-lasting hyaline articular cartilage.

Method used

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  • Small molecules that enable cartilage rejuvenation
  • Small molecules that enable cartilage rejuvenation
  • Small molecules that enable cartilage rejuvenation

Examples

Experimental program
Comparison scheme
Effect test

embodiment p1

[0334]A method for activating a proliferative program in competent adult chondrocytes, said method comprising contacting a competent adult chondrocyte with an activating compound, said activating compound capable of increasing expression of p-STAT3 and c-Myc in said competent adult chondrocyte.

embodiment p2

[0335]The method according to embodiment P1, wherein said activating compound has the structure of Formulae (PI):

[0336]

wherein R1 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R2 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R3 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or Formula (PII):

[0337]

wherein R4 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl,...

embodiment p3

[0338]The method according to embodiment P2, wherein said activating compound has the structure of Formula (PIa):

[0339]

wherein n is an integer from 0 to 5; and R6 at each occurrence is independently halogen, —CF3, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2Cl, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC═(O)NHNH2, —NHC═(O) NH2, —NHSO2H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

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Abstract

There are provided, inter alia, methods and compounds for activating a proliferative program in competent adult chondrocytes.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 126,010, filed Feb. 27, 2015, which is hereby incorporated by reference in its entirety for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]This invention was made with Government support under Grant W81XWH-13-1-0465 awarded by the U.S. Army, Medical Research and Materiel Command. The government has certain rights in the present invention.REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII FILE[0003]The Sequence Listing written in file 48539_516001 WO_ST25.TXT, created Feb. 29, 2016, 8,611 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference.BACKGROUND OF THE INVENTION[0004]Articular cartilage is a highly specialized tissue formed from chondrocytes that protects the bones of diarthrodial joints from forces as...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): C07D277/42C07D417/04
CPCC07D277/42C07D417/04A61P19/00A61K31/427
Inventor EVSEENKO, DENISVAN HANDEL, BENJAMIN J.JOHN, VARGHESE
Owner RGT UNIV OF CALIFORNIA
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